dbSNP rs112563864: TMEM269:p.Ser93Leu (chr1-42793739-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001354602.2(TMEM269):c.278C>T(p.Ser93Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000348 in 1,550,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

TMEM269
NM_001354602.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.53

Publications

0 publications found

Variant links:

Genes affected

TMEM269 (HGNC:52381): (transmembrane protein 269) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM269 links:

ENSG00000283580 (HGNC:):

ENSG00000283580 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25182134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TMEM269	NM_001354602.2 link	c.278C>T	p.Ser93Leu	missense_variant	Exon 4 of 6	ENST00000637012.2	NP_001341531.2
LOC107984946	XR_001738020.2 link	n.-73G>A		upstream_gene_variant
LOC107984946	XR_007066036.1 link	n.-70G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM269	ENST00000637012.2 link	c.278C>T	p.Ser93Leu	missense_variant	Exon 4 of 6	5	NM_001354602.2	ENSP00000490213.1		A0A1B0GVZ9

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000671

AC:

AN:

149134

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1397818

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

689460

show subpopulations

African (AFR)

AF:

0.000697

AC:

AN:

31584

American (AMR)

AF:

0.0000280

AC:

AN:

35658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25122

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35718

South Asian (SAS)

AF:

0.00

AC:

AN:

79166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48188

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078710

Other (OTH)

AF:

0.000190

AC:

AN:

57978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41576

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000102

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 30, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.404C>T (p.S135L) alteration is located in exon 5 (coding exon 4) of the LOC100129924 gene. This alteration results from a C to T substitution at nucleotide position 404, causing the serine (S) at amino acid position 135 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_noAF

Pathogenic

0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.73

PhyloP100

6.5

PrimateAI

Benign

0.41

REVEL

Benign

0.21

GERP RS

5.5

Varity_R

0.24

gMVP

0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs112563864

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over